Enfortumab vedotin improves efficacy outcomes in locally advanced or metastatic urothelial cancer across all exposure quartiles

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Published: 4 Jun 2024
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Prof Daniel Petrylak - Yale School of Medicine, New Haven, USA

Prof Daniel Petrylak speaks to ecancer at ASCO 2024 about a study he presented on the impact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer.

This analysis evaluates the association between enfortumab vedotin plasma exposure, which is impacted by dose modifications, and safety and efficacy outcomes.

Prof Petrylak reports that enfortumab vedotin improved progression-free survival and overall survival outcomes vs chemotherapy in patients across all exposure quartiles.

Enfortumab vedotin improves efficacy outcomes in locally advanced or metastatic urothelial cancer across all exposure quartiles

Prof Daniel Petrylak - Yale School of Medicine, New Haven, USA

The study was to evaluate the pharmacokinetics and toxicity of patients treated with enfortumab vedotin as a single agent. We took data, or pooled data, from several different clinical trials, EV-101, 201 and 301, 301 was the trial that enfortumab was approved for patients who had received prior immune therapy and prior chemotherapy. 201 was the phase II trial and 101 was the phase I dose-finding trial.

We looked at this in terms of toxicities and the overall pharmacokinetics. We drew drug levels in the first two cycles. What we found was that the important thing is to go with full dose at the beginning of treatment, so within the first two cycles you want to administer full doses of enfortumab. If it’s appropriate to reduce toxicities you can dose reduce, it has less of an effect if we dose reduce after that initial period rather than dose reducing and starting at, let’s say, for example 1mg/kg rather than the recommended 1.25mg/kg.

We also analysed data in terms of the onset of toxicities. We found that skin rash and diabetes occurred very, very early in the course of treatment. Peripheral neuropathy occurred much, much later. If we look at the ability to achieve full doses in patients who were responding, that was basically about 7 months after the initiation of treatment; half of patients stayed on full dose.

So, in summary, it’s better to maintain full dose at the beginning and, if it’s appropriate, dose adjust if there is toxicity.

What is next for the study?

Some of the things that are being looked at or are being planned are, of course, is there any difference when you combine enfortumab with pembrolizumab. That’s a little more of a complex issue because you have two different drugs with differing toxicities. So the important thing to know is what’s the minimal effective dose of enfortumab. We see here that it’s important that we give full dose at the beginning. Again, I think that there are future studies looking at other combinations and looking at the pharmacokinetics in terms of toxicity management.